Intravenous sodium valproate versus prochlorperazine for the emergency department treatment of acute migraine headaches: a prospective, randomized, double-blind trial

Ann Emerg Med. 2003 Jun;41(6):847-53. doi: 10.1067/mem.2003.195.


Study objective: We compare the efficacy of intravenous sodium valproate versus prochlorperazine for the emergency department treatment of acute migraine headache.

Methods: We performed a randomized, prospective, double-blind trial performed at a tertiary care military ED. Forty patients, aged 18 to 65 years, presenting with typical migraine symptoms were enrolled. Patients were randomized to receive either 10 mg of prochlorperazine or 500 mg of valproate intravenously over 2 minutes. Pain, nausea, and sedation were assessed by using a standard visual analog scale (VAS). Changes in VAS scores were compared between groups from baseline to end point by using a rank sum test, over time by using 2-way repeated-measures analysis of variance, and by requirement for rescue at 60 minutes by using the Fisher exact test.

Results: Comparison of the change in median VAS scores over 60 minutes revealed that sodium valproate was significantly less effective than prochlorperazine in reducing pain or nausea (P <.001). Median improvements in VAS pain scores (binomial confidence intervals) were as follows: 64.5 mm (48.1 to 75.6 mm) for prochlorperazine versus 9 mm (-3 to 39.6 mm) for sodium valproate. Median improvements in VAS nausea scores were as follows: 35.5 mm (13.2 to 47.9 mm) for prochlorperazine versus 2 mm (-1.3 to 11 mm) for sodium valproate. There was no significant difference (P =.603) detected in the median changes in VAS scores for sedation: -4 mm (-29.9 to 8.6 mm) for prochlorperazine versus 0 mm (-6.6 to 6 mm) for sodium valproate. Comparison of the mean VAS time curves for pain and nausea also demonstrated a significant difference (both P <.001) but not for sedation (P =.232). In post hoc analysis, valproate failed to elicit significant improvement in pain or nausea scores over time, whereas prochlorperazine improved pain by 30 minutes (P <.001) and nausea by 15 minutes (P =.002). At the conclusion of the study, 15 (79%) of 19 patients receiving valproate required rescue treatment compared with 5 (25%) of 20 patients receiving prochlorperazine (P <.001).

Conclusion: Prochlorperazine was statistically and clinically superior to sodium valproate for the treatment of the pain and nausea associated with acute migraine headaches.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Anticonvulsants / therapeutic use*
  • Antiemetics / therapeutic use*
  • Double-Blind Method
  • Emergency Service, Hospital
  • Female
  • Humans
  • Male
  • Middle Aged
  • Migraine Disorders / complications
  • Migraine Disorders / drug therapy*
  • Nausea / etiology
  • Nausea / prevention & control
  • Pain Measurement
  • Prochlorperazine / therapeutic use*
  • Prospective Studies
  • Treatment Outcome
  • Valproic Acid / therapeutic use*


  • Anticonvulsants
  • Antiemetics
  • Valproic Acid
  • Prochlorperazine